Skin lesions, such as warts and benign tumors, are very common in humans and often virally-induced. There are a variety of double stranded DNA (dsDNA) viruses that are the cause of skin lesions, each virus being related to a specific clinical presentation. Among the dsDNA wart-causing viruses are the herpesviridae (30 types), papillomaviridae (107 types), and the poxviridae (17 types). Viruses also induce tumors in mammals, for example, many of the known types of human papillomaviruses (HPV). Some of these HPV's have been associated with benign tumors, such as common warts, while others have been implicated as etiologic agents in dysplasia and carcinomas in the oral and genital mucosa.
Viral-induced warts are typically infectious and can be auto inoculated and spread to other individuals by direct contact. Numerous types of warts are observed in humans, including verrucae warts, plantar warts, flat warts, and genital warts. Verrucae warts have a rough surface, are lumpy, and typically flesh colored. Finger-like projections and sometimes dark specks are present, which are the result of thrombosed capillaries. Plantar warts are found on the planter surface of the feet and can be deep and painful. These warts occur singularly, in clusters or can be spread over a wide area. Flat warts are typically small, flat-topped, flesh colored papules that occur primarily on the face, hands, and forearms. Usually the surface of the wart is smooth and they may appear in the hundreds. Genital warts are soft, flesh colored or slightly pigmented, occur in the genitalia of the mammal, and are sexually transmitted. Chronic infections with the viruses that cause genital warts in women are a serious problem as intra epithelial neoplasia or squamous cell carcinoma may develop. See Oski et al., Princ. Pract. Pediatrics, 2nd Ed., pp. 789-790, Lippincott Williams & Wilkins (1994).
Another example of a viral-induced skin lesion are the lesions caused by Molluscum contagiosum (MC). MC virus is a member of the poxvirus group. It is a large dsDNA virus that replicates in the cytoplasm of infected cells. Skin lesions caused by MC have an incidence of approximately 1/200 children by the age of 10 in the United States. While the disease may be epidemic in children, it occurs in people of all ages and is worldwide in distribution. In adults, the infection may be spread by sexual contact. Skin lesions caused by MC are characterized by the appearance on the body surface of small, discreet, lobulated epidermal outgrowths or lesions that occur throughout the body. These lesions, which are the result of excessive cellular proliferation stimulated in the keratinocyte layer by virus that has entered through the skin, are discrete pearly white or flesh colored papules that may persist for up to three years. The lesions may have a central pore, which contains within its center dead skin cells and numerous virus particles.
Infections caused by MC commonly last for 9-18 months but the condition can in certain cases persist for as long as 3-4 years. During this time, new crops of lesions appear, each lesion growing slowly for 6-12 weeks and persisting for an average of 3-4 months.
At present there is no drug treatment for MC; the virus is resistant to the commonly used anti-viral agents which are effective in treating other viral infections and the disease is treated only by surgical removal of the lesions, e.g. cryotherapy, or tissue destruction by chemical or physical means. This can be painful and distressing, particularly for children, and does not prevent the reappearance of fresh lesions.
Recently, it has also been observed that individuals with depressed immune systems, such as sufferers of Acquired Immune Deficiency Syndrome (AIDS), are prone to Molluscum contagiosum and HPV viral skin infections that can result in tumor growth recalcitrant to treatment, resulting in mental and physical distress to the afflicted individual (Tyring S. K., Am J Obstet Gynecol. 189 (3 Suppl):S12-6 (2003)).
Skin lesions are presently treated by various therapies, but none are considered truly effective as they typically fail to totally cure the lesions and do not prevent recurrence. A discussion of presently accepted therapies can be found in Stone, Cl. Infec. Diseases, Suppl. 20:991-997 (1995) and in Sterling, Practioner, 239(1546):44-47 (1995). One product presently marketed for wart removal is OCCLUSAL®-HP, marketed by the GenDerm Corporation of Lincolnshire, Ill. This product is a 17% solution of salicylic acid in a polyacrylic vehicle. Another wart removal product DUO FILM®, by the Shering-Plough Company of Memphis, Tenn. is a patch containing 40% salicylic acid. The product literature recommends that the wart be washed and dried prior to the application of a medicated patch. This patch is then covered with an additional bandage and the procedure is repeated every 48 hours until the wart is gone, which sometimes takes up to 12 weeks.
More generally, these and other current modalities for the treatment of viral-induced tumors and warts depend on tissue destruction or the removal of the tumor or wart by either: (1) surgical intervention (laser or operative); (2) the application of organic acids, such as glacial acetic acid and/or salicylic acid and lactic acid to “burn” the tumor away; (3) the use of a drug such as podophyllin, interferon, and fluorouracil or 5-fluorouracil; and/or (5) freezing. While being useful for removing the viral-induced growth, these treatment modalities still suffer from one or more of the following drawbacks: (1) they can result in the destruction of healthy uninfected tissue; (2) they can result in scarring and disfigurement; (3) they can result in discomfort to the person being treated thereby; (4) they can result in necrosis of the tumor and the surrounding tissue that can result in a secondary infection requiring treatment with an antibiotic; and (5) they do not result in the destruction of latent viral DNA which may be maintained in surrounding tissues. Furthermore with these conventional treatments, subjects suffer from significant local, and at times, systemic side effects, incomplete resolution, and frequent recurrences and of course, a monetary expense for continued treatment.